Cardiovascular Risk Reduction Research Articles

Intensive Blood Pressure Lowering in Individuals With Low Diastolic Blood Pressure and Elevated Troponin Levels in SPRINT.

Among individuals with hypertension and low diastolic blood pressure (DBP), the optimal BP target remains controversial due to concerns that BP lowering may reduce coronary perfusion. We determined the impact of intensive BP control among individuals with elevated systolic BP who have low DBP and elevated hs-cTnT (high-sensitivity cardiac troponin T) levels. A total of 8828 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were stratified by baseline DBP. Those with low DBP (<70 mm Hg) were further stratified by elevated hs-cTnT (≥14 ng/L) at baseline. The effects of intensive versus standard BP lowering on a cardiovascular disease composite end point, all-cause death, and 1-year change in hs-cTnT were determined. The combination of low DBP/high hs-cTnT was independently associated with a higher risk for cardiovascular disease and all-cause death, as well as greater 1-year increases in hs-cTnT, compared with DBP ≥70 mm Hg. However, randomization to intensive versus standard BP lowering led to similar reductions in cardiovascular disease risk among individuals with low DBP/high hs-cTnT (hazard ratio [HR], 0.82 [95% CI, 0.57-1.19]), low DBP/low hs-cTnT (HR, 0.48 [95% CI, 0.29-0.79]), and DBP ≥70 mm Hg (HR, 0.73 [95% CI, 0.60-0.89]; P for interaction=0.20). Intensive BP lowering also led to a reduction in all-cause death that was similar across groups (P for interaction=0.57). In this nonprespecified subgroup analysis of SPRINT, individuals with low DBP and elevated hs-cTnT, low DBP and nonelevated hs-cTnT, and DBP ≥70 mm Hg derived similar cardiovascular disease and mortality benefits from intensive BP lowering. These findings warrant confirmation in other studies.

O57: Tailored risk assessment and forecasting in intermittent claudication using machine learning (TRAFIC-ML)

Abstract Introduction Guidelines recommend cardiovascular risk reduction and supervised exercise therapy as the initial treatment for patients with intermittent claudication(IC). However, implementation challenges and poor patient compliance lead to significant variation in management and therefore outcomes. We propose a precise machine learning derived decision support system that aims to provide personalised outcome predictions across different management strategies. Methods Feature selection was performed using the least absolute shrinkage and selection operator method. The model was developed using a bootstrapped sample of 10,000 patients based on 255 patients from our vascular centre. The model considered 27 baseline characteristics, compliance to best medical therapy/smoking cessation and treatment strategy. The model was validated using a separate dataset of 254 patients. This model was then used to build a prototype interactive decision support system which was evaluated using calibration curves, decision curve analyses and area under the receiver operator characteristic (AUROC) curves. Results The AUROC curves demonstrated excellent discrimination for the risk of progression to chronic limb threatening ischaemia at two years(0.892) and five years(0.866) and likelihood of major adverse cardiovascular events(0.836), major adverse limb events(0.891) and revascularisation(0.896)within 5 years, regardless of the treatment strategy. Calibration curves demonstrated good consistency between predicted and actual outcomes and decision curve analyses confirmed clinical utility. The tool maintained an accuracy of &amp;gt;80% and an effect size of &amp;gt;0.5. Conclusion Our decision support system successfully predicts outcomes in IC regardless of treatment strategy, offering potential for improved risk stratification and patient outcomes.

Effect of statin add-on therapy on cardiovascular mortality.

Cardiovascular (CV) disease remains a leading cause of mortality despite statin therapy. Statin add-on lipid-lowering therapies have been investigated for CV risk reduction, but their effect on CV mortality has not been reviewed. This review describes CV outcomes trials of add-on therapies to statins, highlighting findings related to the primary composite CV endpoints and the more patient-centric endpoint of CV-related mortality. Add-on ezetimibe met its primary composite CV endpoint vs. statin alone (P = 0.016); however, the individual endpoint of death from CV causes did not differ between groups. Add-on therapy with proprotein convertase subtilisin/kexin type 9 inhibitors achieved the primary composite CV endpoints in the respective CV outcomes trials for alirocumab (P < 0.001) and evolocumab (P < 0.001); however, neither CV outcomes trial found a difference vs. placebo in CV-related mortality. In its CV outcomes trial, icosapent ethyl added to statin therapy significantly reduced the occurrence of the primary composite CV endpoint (P < 0.001) and the individual endpoint of risk of CV-related death (P = 0.03) vs. placebo. A CV outcomes trial of bempedoic acid monotherapy achieved its primary composite CV endpoint vs. placebo (P = 0.004) but not the endpoint of death from CV causes. Statin add-on therapies achieved their CV outcomes trial composite CV endpoints. Proprotein convertase subtilisin/kexin type 9 inhibitors and icosapent ethyl have approved indications for CV risk reduction. Only add-on therapy with icosapent ethyl demonstrated a significant reduction in CV mortality in the overall intent-to-treat population, possibly due to the unique pleiotropic mechanisms of eicosapentaenoic acid independent of lipid-lowering effects.

Exploring determinants of sex and family history-based disparity in type 2 diabetes mellitus prevalence among clinical patients

BackgroundType 2 diabetes mellitus represents a multifaceted disorder characterized by intricate pathophysiological mechanisms, encompassing diminished insulin secretion, augmented hepatic glucose production, and heightened insulin resistance. This study aims to assess the sex (Male and Female only) and family history-based differences in the prevalence of T2DM and explore the determinants contributing to this disparity among clinical patients.Subjects and methodsThe study encompassed a diverse pool of clinical patients, encompassing both individuals with diabetes and those without the condition, who had previously sought medical attention for clinical checkups at healthcare centers. The collected data included essential parameters such as blood pressure, weight, height, smoking habits, educational background, and physical activity levels. To ensure methodological rigor and data accuracy, blood pressure measurements adhered to the stringent guidelines set forth by the World Health Organization.ResultsParticipants of the present study reported diabetes, among which notable findings emerged regarding health indicators. It was observed that the prevalence of high blood pressure, obesity, and high blood cholesterol exhibited a statistically significant increase among the female participants, underscoring the sex-based disparities in these health parameters. The male population aged 60 or older, the presence of a family history of DM accentuated this risk, resulting in a striking 3.1 times higher prevalence compared to females, who exhibited a 2.4 times higher risk (OR = 2.4, p = 0.0008). This intriguing relationship between diabetes and cholesterol levels was not limited to sex. Both male (OR = 2.47) and female (OR = 2.1) diabetes patients displayed highly significant associations with cholesterol levels. The risk of T2DM was significantly associated with triglycerides in both sexes (1.58 times higher in males, and 1.71 times higher in females).ConclusionsThe significance of hypertension as a comorbidity in T2DM, highlighting sex-specific associations and the potential impact of a family history of diabetes on blood pressure. Our findings emphasize the importance of considering lipid profiles, obesity, and their sex-specific associations when assessing and managing diabetes risk. Comprehensive diabetes care should include strategies for lipid control, weight management, and cardiovascular risk reduction, tailored to the individual’s sex and specific risk profile.

Prevention and treatment of hypertensive left ventricular hypertrophy.

Left ventricular (LV) hypertrophy (LVH) is a well recognized target organ adaptation to longstanding uncontrolled hypertension and other cardiovascular risk factors. It is also a strong and independent predictor of many cardiovascular disorders. This focused review explores the current concepts in screening, diagnosis, prevention, and treatment of LVH in patients with hypertension. Currently, the primary screening and diagnostic tools for LVH are ECG and 2D echocardiography. Implementing machine learning in the diagnostic modalities can improve sensitivity in the detection of LVH. Lifestyle modifications, blood pressure control with antihypertensive therapy, and management of comorbidities aid in preventing and reversing LV remodeling. LVH is a common and often silent complication of hypertension. Prevention and reversal of LV remodeling are crucial for cardiovascular risk reduction in patients with hypertension.

RNA Interference-based Therapies for the Reduction of Cardiovascular Risk.

Globally, there remains an unwavering increase in the incidence of cvd - from 271 million in 1990 to 523 million in 2019. Among the several modifiable and non-modifiable risk factors of heart disease, dyslipidemia is an important and prevalent risk factor mediated by both genetics and lifestyle factors. Hence, lowering lipid levels, specifically, ldl-c levels (low-density lipoprotein cholesterol), is a key strategy in decreasing the risk of cardiovascular disease. A reduction of 20 mg/dl in ldl-c levels has been found to prevent 2-3 cases of coronary artery disease (cad) for every 1000 individuals. Studies have also found reductions in ldl-c levels to be associated with a mortality benefit. However, ldl-c levels reduction may not eliminate the risk of significant cardiovascular events.

Effect of Combined Physical Exercise Training in Reducing Cardiovascular Risk Among Adults with Obesity: A Randomized Clinical Trial.

It is necessary to understand the relationship between different models of exercise periodization and the reduction of cardiovascular risk in adults with obesity. The aim of this study was to verify the effect of two periodization models of combined training on the cardiovascular risk of adults with obesity of both sexes. A randomized clinical trial was conducted with adults of both sexes with obesity. They were divided into three groups: control group (CG), non-periodized combined training group (NG), and combined training group with linear periodization (PG). The NG and PG groups underwent physical exercise training regimen for 16 weeks, in three weekly sessions of 60min each, with the volume and intensity equalized. Cardiovascular risk was measured by the overall Framingham risk score (FRS). Generalized estimation equations and individual responsiveness analyses were used, stratified by sex. A statistically significant reduction in FRS was observed only in men of the NG (pre: 2.50 ± 0.56; post: 0.50 ± 1.02; p-value = 0.001). There was no statistically significant intervention effect on the women's cardiovascular risk. It was found that, regardless of sex, subjects in the control group mostly presented results of increased cardiovascular risk. In contrast, those belonging to the exercise groups, if not reduced, at least stabilized the chances of suffering a cardiovascular event in the next ten years after 16 weeks of combined training. Sixteen weeks of non-periodized combined training were sufficient to reduce cardiovascular risk in men with obesity. Both periodization models were important to stabilize the risk of developing a cardiovascular disease in the next 10 years.

The Pink Tax: Sex and Gender Disparities in Peripheral Artery Disease

Peripheral artery disease (PAD) is an atherosclerotic disease associated with significant functional impairment, morbidity, and mortality. Among women, PAD remains poorly recognized and undermanaged. Compared with men, women with PAD tend to be underdiagnosed or misdiagnosed, have poorer quality of life, and experience higher rates of PAD-related morbidity and cardiovascular mortality. In this review, we describe the sex- and gender-related differences in the epidemiology, presentation, diagnosis, and management of PAD. We provide specific recommendations to overcome these factors, including greater awareness and an increased emphasis on tailored and more aggressive interventions for women with PAD. Such changes are warranted and necessary to achieve more equitable outcomes in women with PAD, including improved limb outcomes, enhanced lifestyle, and cardiovascular risk reduction.

Factors Associated with Delayed Care Among Women Veterans Actively Engaged in Primary Care.

Background: Delaying needed medical care contributes to greater health risks and higher long-term medical costs. Women Veterans with complex medical and mental health needs face increased barriers to timely care access. Objectives: In a sample of women Veterans with recent engagement in Veterans Administration (VA) primary care, we aimed to compare characteristics of women Veterans who delayed care in the past 6 months with those who did not and examine factors associated with self-reported delayed care. Our study aims to inform interventions focused on eliminating health care access disparities among women Veterans. Materials and Methods: An innovation to improve women Veterans' engagement and retention in evidence-based health care for cardiovascular (CV) risk reduction (CV Toolkit) was implemented across five primary care sites within the VA. Women Veterans who were exposed to at least one CV Toolkit component participated in a mailed survey (n = 253). We used multivariate logistic regression to model factors associated with delaying care, including trust in VA providers, positive mental health screening (i.e., positive screen for either depression or anxiety), traumatic experience, self-rated health, and age. Results: Women with any mental health symptoms (odds ratio [OR] 2.42, 95% confidence interval [CI]: 1.23-4.74) and women who had experienced a traumatic event (OR 2.61, 95%CI: 1.11-6.14) were significantly more likely to report delaying care. Conclusions: Our study identified high rates of delayed care-over one-third of respondents-among women Veterans with recent primary care engagement. Mental health symptoms were the most common reported reason for delay among those who delayed care. Clinical Trial registration: NCT02991534.

Circulating MicroRNA-19 and cardiovascular risk reduction in response to weight-loss diets

MicroRNA-19 (miR-19) plays a critical role in cardiac development and cardiovascular disease (CVD). We examined whether change in circulating miR-19 was associated with change in CVD risk during weight loss. This study included 509 participants with overweight or obesity from the 24-month weight-loss diet intervention study (the POUNDS Lost trial) and with available data on circulating miR-19a-3p and miR-19b-3p at baseline and 6 months. The primary outcome for this analysis was the change in atherosclerotic CVD (ASCVD) risk at 6 and 24 months, which estimates the 10-year probability of hard ASCVD events. Secondary outcomes were the changes in ASCVD risk score components. Circulating miR-19a-3p and miR-19b-3p levels significantly decreased during the initial 6-month dietary intervention period (P=0.008, 0.0004, respectively). We found that a greater decrease in miR-19a-3p or miR-19b-3p was related to a greater reduction in ASCVD risk (β[SE]=0.33 [0.13], P=0.01 for miR-19a-3p; β[SE]=0.3 [0.12], P=0.017 for miR-19b-3p) over 6 months, independent of concurrent weight loss. Moreover, we found significant interactions between change in miR-19 and sleep disturbance on change in ASCVD risk over 24 months of intervention (P interaction=0.01 and 0.008 for miR-19a-3p and miR-19b-3p, respectively). Participants with a greater decrease in miR-19 without sleep disturbance had a greater reduction of ASCVD risk than those with slight/moderate/great amounts of sleep disturbance. In addition, change in physical activity significantly modified the associations between change in miR-19 and change in ASCVD risk over 24 months (P interaction=0.006 and 0.004 for miR-19a-3p and miR-19b-3p, respectively). A greater decrease in miR-19 was significantly associated with a greater reduction in ASCVD risk among participants with an increase in physical activity, while non-significant inverse associations were observed among those without an increase in physical activity. In conclusion, decreased circulating miR-19 levels during dietary weight-loss interventions were related to a significant reduction in ASCVD risk, and these associations were more evident in people with no sleep disturbance or increase in physical activity. ClinicalTrials.gov NCT00072995.

Is there a role for earlier use of combination therapy?

As the global population ages and cardiovascular risk factors rise, we can expect a continued increase in atherosclerotic disease. Low-density lipoprotein cholesterol (LDL-C) reduction is a cornerstone of cardiovascular risk reduction with strong, causal evidence indicating that the greatest benefit is derived from early and large decreases in LDL-C. Despite the adoption of statins as the backbone of lipid-therapy regimens, numerous studies and registry analyses reveal our collective inability to achieve LDL-C goals in high-risk patients. Combination therapy with ezetimibe has been shown to result in statistically significant decreases in LDL-C level, atheroma volume, and cardiovascular adverse event rates. A major barrier to implementing an upfront combination therapy approach is the perceived side effects from therapeutic agents although multiple studies show that a therapeutic patient-physician relationship could overcome this issue. Novel agents such as PCSK-9 inhibitors, bempedoic acid, and inclisiran have the potential to achieve similar outcomes although additional research is needed regarding the cost effectiveness of these approaches. Despite these hurdles, there is a role for the newer agents early in the disease course of high-risk patients such as those with markedly elevated LDL-C >190 mg/dL and FH.The implementation of upfront combination therapy, especially in high-risk patients, will decrease clinical inertia while allowing for earlier consideration of newer, effective agents to decrease cardiovascular burden.

Impact of the 2021 European Society for Cardiology prevention guideline's stepwise approach for cardiovascular risk factor treatment in patients with established atherosclerotic cardiovascular disease.

This study aimed to evaluate the stepwise approach for cardiovascular (CV) risk factor treatment as outlined by the European Society for Cardiology 2021 guidelines on CV disease (CVD) prevention in patients with established atherosclerotic CVD (ASCVD). In patients with ASCVD, included in UCC-SMART (n = 8730) and European parts of the REACH registry (n = 18 364), the 10-year CV risk was estimated using SMART2. Treatment effects were derived from meta-analyses and trials. Step 1 recommendations were LDL cholesterol (LDLc) < 1.8 mmol/L, systolic blood pressure (SBP) < 140 mmHg, using any antithrombotic medication, sodium-glucose co-transporter 2 (SGLT2) inhibition, and smoking cessation. Step 2 recommendations were LDLc < 1.4 mmol/L, SBP < 130 mmHg, dual-pathway inhibition (DPI, aspirin plus low-dose rivaroxaban), colchicine, glucagon-like peptide (GLP)-1 receptor agonists, and eicosapentaenoic acid. Step 2 was modelled accounting for Step 1 non-attainment. With current treatment, residual CV risk was 22%, 32%, and 60% in the low, moderate, and pooled (very) high European risk regions, respectively. Step 2 could prevent up to 198, 223 and 245 events per 1000 patients treated, respectively. Intensified LDLc reduction, colchicine, and DPI could be applied to most patients, preventing up to 57, 74, and 59 events per 1000 patients treated, respectively. Following Step 2, the number of patients with a CV risk of <10% could increase from 20%, 6.4%, and 0.5%, following Step 1, to 63%, 48%, and 12%, in the respective risk regions. With current treatment, residual CV risk in patients with ASCVD remains high across all European risk regions. The intensified Step 2 treatment options result in marked further reduction of residual CV risk in patients with established ASCVD. Guideline-recommended intensive treatment of patients with cardiovascular disease could prevent additional 198-245 new cardiovascular events for every 1000 patients treated.

Prediabetes and Cardiometabolic Risk: The Need for Improved Diagnostic Strategies and Treatment to Prevent Diabetes and Cardiovascular Disease.

The progression from prediabetes to type-2 diabetes depends on multiple pathophysiological, clinical, and epidemiological factors that generally overlap. Both insulin resistance and decreased insulin secretion are considered to be the main causes. The diagnosis and approach to the prediabetic patient are heterogeneous. There is no agreement on the diagnostic criteria to identify prediabetic subjects or the approach to those with insufficient responses to treatment, with respect to regression to normal glycemic values or the prevention of complications. The stratification of prediabetic patients, considering the indicators of impaired fasting glucose, impaired glucose tolerance, or HbA1c, can help to identify the sub-phenotypes of subjects at risk for T2DM. However, considering other associated risk factors, such as impaired lipid profiles, or risk scores, such as the Finnish Diabetes Risk Score, may improve classification. Nevertheless, we still do not have enough information regarding cardiovascular risk reduction. The sub-phenotyping of subjects with prediabetes may provide an opportunity to improve the screening and management of cardiometabolic risk in subjects with prediabetes.

Healthy immigrant community study protocol: A randomized controlled trial of a social network intervention for cardiovascular risk reduction among Hispanic and Somali adults

BackgroundImmigrants to the United States face structural barriers that contribute to rising cardiovascular risk factors and obesity after immigration. This manuscript describes the development of the Healthy Immigrant Community protocol and baseline measures for a stepped wedge cluster randomized trial to test the effectiveness of a social network intervention for cardiovascular risk reduction among two immigrant populations. MethodsWe developed a social network-informed, community-based, participatory research-derived health promotion intervention with Hispanic and Somali immigrant communities in Minnesota consisting of mentoring, educational and motivational sessions, group activities, and a community toolkit for healthy weight loss delivered by culturally concordant health promoters (HPs) to their social networks. Using a stepped wedge cluster randomized design, social network-based groups were randomly assigned to receive the intervention either immediately or after a delay of one year. Outcomes, measured at baseline, 6 months, 12 months, and 24 months, were derived from the American Heart Association's “Life's Simple 7”: BMI and waist circumference, blood pressure, fasting blood glucose, total cholesterol, physical activity level, and dietary quality. ResultsA total of 51 HPs were enrolled and randomized (29 Hispanic; 22 Somali). There were 475 participants enrolled in the study, representing a mean social network group size of 8 (range, 5–12). The mean BMI of the sample (32.2) was in the “obese” range. ConclusionProcesses and products from this Healthy Immigrant Community protocol are relevant to other communities seeking to reduce cardiovascular risk factors and negative health behaviors among immigrant populations by leveraging the influence of their social networks.

Development of delivery indicators and delivery enablers for cardiovascular disease in the UK: a modified Delphi study

IntroductionStandards to define and measure quality in healthcare for cardiovascular disease risk reduction and secondary prevention are available, but there is a paucity of indicators that could serve as facilitators...

P 025: A real-world evaluation of the cardiovascular risk reduction clinic (CRRC) at Hospital Pulau Pinang: A comprehensive analysis

P 025: A real-world evaluation of the cardiovascular risk reduction clinic (CRRC) at Hospital Pulau Pinang: A comprehensive analysis

Abstract TMP106: Use of Net Promoter Score to Quantify the Participant Experience With a Telehealth Lifestyle Management and Cardiovascular Risk Reduction Coaching Program

Introduction: Improving the patient experience of care is 1 of the 3 dimensions of healthcare’s “Triple Aim.” The net promoter score (NPS) measures willingness to recommend a company’s services and is widely used by Fortune 500 companies as an indicator of customer loyalty/satisfaction. The NPS is increasingly being used to assess patients’ healthcare experience. We sought to quantify the experience of participants in the same telehealth lifestyle management and CVD risk reduction coaching program used in multiple NIH/PCORI-funded stroke-related multi-center RCTs (namely, SAMMPRIS, CREST-2, CAPTIVA and TEAMS-BP) by measuring the NPS in real-world (i.e., non-RCT) program participants. Methods: Participants in the coaching program typically have an opportunity to complete a voluntary satisfaction survey after 12 weeks and 1 year of participation and annually thereafter. The survey is conducted online or via telephone. For this analysis the NPS was calculated, from 17,929 consecutive surveys completed by non-RCT program participants, using responses on an 11-point scale (10 = "strongly agree"; 0 = "strongly disagree") to this item: “I would recommend the program to others.” Scores can range from -100 (worst) to +100 (best). In industry, a positive NPS is well regarded, and scores ≥50 are thought to highlight an excellent experience. Results: Three categories of responders were identified and classified as ‘promoters’ (rating = 9 or 10; i.e., those who would likely recommend the program = 78% of responses), ‘passives’ (rating = 7 or 8; i.e., those who are satisfied but would probably not actively promote the program = 16% of responses) and ‘detractors’ (rating = ≤6; i.e., those who might actively discourage participation = 6% of responses). The NPS (calculated from the % of promoters minus the % of detractors) was +72, a score comparable to that achieved by the most popular/successful commercial organizations in other industries. Conclusion: This is the first study to utilize the NPS to evaluate the participant experience with a telehealth coaching program that has been/is currently being successfully deployed in multiple stroke-related multi-center RCTs. The data show that real-world program participants have an NPS indicative of very high satisfaction.

Improving cardiovascular health in patients with an abdominal aortic aneurysm: development of the cardiovascular risk reduction in patients with aneurysms (CRISP) behaviour change intervention

BackgroundAbdominal aortic aneurysm (AAA) is an important cardiovascular health problem. Ultrasound screening is proven to reduce AAA mortality and programmes have been implemented in some healthcare systems. Those who are identified as having a small AAA in screening enter into a surveillance programme to monitor AAA size. Individuals in AAA surveillance are at elevated risk of cardiovascular events, which is not currently addressed sufficiently. We aimed to develop a simple intervention to reduce cardiovascular risk, which could be embedded in AAA surveillance pathways.MethodsIntervention mapping methods were used to co-develop the intervention with individuals with AAA, families/carers, and healthcare staff. We identified “targets for change” by synthesising research evidence and international guidelines and consulting with patients, caregivers and health service providers. We conducted a series of workshops to identify barriers to and facilitators of change and used taxonomies of behaviour change theories and techniques to match intervention strategies to each target. Further stakeholder involvement work helped refine the intervention.ResultsThe developed intervention focusses on assessment and individually tailored discussion of risk factors, exchanging information, building motivation and action planning, followed by review of progress and problem-solving. Workbooks covering physical activity, diet, stress management, alcohol, smoking, blood pressure and mental health are provided to support behaviour change. The intervention is facilitated by trained healthcare professionals during the patient’s AAA screening appointment for the duration that they are in surveillance.DiscussionThe developed intervention will now be tested to assess whether it can be integrated with the current AAA screening programme. The developed intervention is a novel approach to reducing cardiovascular disease in the AAA population, it is also the first intervention which tries to do this in this population.Trial registrationInternational Clinical Trial Registration: ISRCTN93993995.

Real-World Risk of Recurrent Cardiovascular Events in Atherosclerotic Cardiovascular Disease Patients with LDL-C Above Guideline-Recommended Threshold: A Retrospective Observational Study.

The 2021 Canadian Cardiovascular Society (CCS) guidelines recommend intensive low-density lipoprotein cholesterol (LDL-C) reduction for patients with atherosclerotic cardiovascular disease (ASCVD). For patients above LDL-C threshold on maximally tolerated statins, adding ezetimibe and/or a proprotein convertase subtilisin/kexin type9 inhibitor (PCSK9i) is recommended. This population-based, real-world study examined cardiovascular (CV) events in patients with ASCVD who are on statins and above current guideline threshold LDL-C levels. Using administrative health data in Alberta, Canada, we identified patients with myocardial infarction (MI), ischemic stroke (IS), or peripheral artery disease with LDL-C > 1.8mmol/L on statins between April 1, 2010 and March 31, 2016. Exploratory subgroups included very high-risk patients with ASCVD shown to derive the most benefit from PCSK9i intensification as identified by the CCS guidelines, including those with acute coronary syndrome (ACS) or recent MI. Frequencies and rates of individual and composite CV events (primary outcome: MI, IS, hospitalization for unstable angina, coronary revascularization, cardiovascular death; secondary outcome: MI, IS, CV death) were calculated over follow-up. The study included 32,984 patients with a mean (standard deviation) follow-up of 40.8 (21.0) months. Overall, 17.7% and 15.6% experienced a primary and secondary outcome, respectively, with rates of 5.58 and 4.83 per 100 patient-years, respectively. CV death and MI were the most common events. Subgroups with recurrent MI and comorbid diabetes exhibited higher CV event rates (23.6% and 22.2% had a primary outcome, respectively). Rates of CV events were notably high in patients with ACS or recent MI (49.4% and 54.0% had a primary outcome, respectively). This real-world study confirms that statin-treated high-risk patients with ASCVD and above-threshold LDL-C levels have substantial incidence of recurrent CV events. These findings reinforce the opportunity for lipid-lowering therapy intensification in high-risk patients to levels below guideline-recommended threshold in order to reduce CV risk.

The vascular response to acute sauna heating is similar in young and middle-aged adults.

Sauna has been linked to a reduction of cardiovascular disease risk and is a promising nonpharmacological treatment for populations at risk of cardiovascular disease. This study examined the vascular response to an acute bout of sauna heating in young and middle-aged individuals. Ten young (25 ± 4 yr, 6 males and 4 females) and eight middle-aged adults (56 ± 4 yr, 4 males and 4 females) underwent 40 min of sauna exposure at 80°C. Esophageal and intramuscular temperatures, brachial and superficial femoral artery blood flow, artery diameter, and shear rates were recorded at baseline and following heat exposure. Brachial artery flow-mediated dilation (FMD) was measured at baseline and following 90 min of recovery. Esophageal and muscle temperatures increased similarly in the young and middle-aged adults by 1.5 ± 0.53 and 1.95 ± 0.70°C, respectively (P < 0.05). The shear rate increased by 170-200% (P < 0.001), while blood flow increased by 180-390% (P < 0.001) in the superficial femoral and brachial arteries, respectively, and did not differ between age groups (P = 0.190-0.899). Systolic blood pressure was reduced from 135 ± 17 to 122 ± 20 mmHg (P = 0.017) in middle-aged participants. These data indicate that young and middle-aged adults have similar vascular responses to acute sauna heating.NEW & NOTEWORTHY Sauna therapy has been shown to improve cardiovascular health and function in older adults and individuals with cardiovascular disease risk factors. Specifically, improvements in vascular function have been reported and have been attributed to the increased hemodynamic stimuli on the vasculature associated with thermal stress. The present study quantified this hemodynamic response to a sauna protocol associated with improved cardiovascular health across the lifespan. Our data show that middle-aged adults have the same shear rate and blood flow response to sauna as young adults.